ABSTRACT
OBJECTIVE: Ketogenic diet is the first line therapy for neurological symptoms associated with pyruvate dehydrogenase deficiency (PDHD) and intractable seizures in a number of disorders, including GLUT1 deficiency syndrome (GLUT1-DS). Because high-fat diet raises serious compliance issues, we investigated if oral L,D-3-hydroxybutyrate administration could be as effective as ketogenic diet in PDHD and GLUT1-DS. METHODS: We designed a partial or total progressive substitution of KD with L,D-3-hydroxybutyrate in three GLUT1-DS and two PDHD patients. RESULTS: In GLUT1-DS patients, we observed clinical deterioration including increased frequency of seizures and myoclonus. In parallel, ketone bodies in CSF decreased after introducing 3-hydroxybutyrate. By contrast, two patients with PDHD showed clinical improvement as dystonic crises and fatigability decreased under basal metabolic conditions. In one of the two PDHD children, 3-hydroxybutyrate has largely replaced the ketogenic diet, with the latter that is mostly resumed only during febrile illness. Positive direct effects on energy metabolism in PDHD patients were suggested by negative correlation between ketonemia and lactatemia (r 2 = 0.59). Moreover, in cultured PDHc-deficient fibroblasts, the increase of CO2 production after 14C-labeled 3-hydroxybutyrate supplementation was consistent with improved Krebs cycle activity. However, except in one patient, ketonemia tended to be lower with 3-hydroxybutyrate administration compared to ketogenic diet. CONCLUSION: 3-hydroxybutyrate may be an adjuvant treatment to ketogenic diet in PDHD but not in GLUT1-DS under basal metabolic conditions. Nevertheless, ketogenic diet is still necessary in PDHD patients during febrile illness.
ABSTRACT
BACKGROUND: Acute decompensation of maple syrup urine disease (MSUD) is usually treated by enteral feeding with an amino-acid mixture without leucine (Leu), valine or isoleucine. However, its administration is ineffective in cases of gastric intolerance and some adult patients refuse enteral feeding via a nasogastric tube. We developed a new parenteral amino-acid mixture for patients with MSUD. METHODS: Seventeen decompensation episodes in four adult patients with MSUD treated with a parenteral amino-acid mixture (group P) were compared to 18 previous episodes in the same patients treated by enteral feeding (group E). RESULTS: The mean Leu concentration at presentation was similar in the groups P and E (1196.9 µmol/L and 1212.2 µmol/L, respectively). The mean decrease in the Leu concentration during the first 3 days of hospitalisation was significantly higher in group P than group E (p = 0.0026); there were no side effects. The mean duration of hospitalisation was similar (4 vs. 4.5 days, p = NS). No patient in group P deteriorated whereas one patient in group E required dialysis. CONCLUSION: This new parenteral amino-acid mixture is safe and allows efficient Leu concentration decrease during acute MSUD decompensation episodes in adults. Its use avoids the need for nasogastric tube insertion.
Subject(s)
Amino Acids/administration & dosage , Heart Failure/diet therapy , Maple Syrup Urine Disease/diet therapy , Parenteral Nutrition , Adult , Female , Food, Formulated , Heart Failure/etiology , Hospitalization , Humans , Male , Maple Syrup Urine Disease/complications , Patient Acceptance of Health Care , Young AdultABSTRACT
Bronchial inhalation of amiloride chlorhydrate has been suggested for a number of years in the treatment of the pulmonary disease in cystic fibrosis. However, physiotherapy remains invaluable in the struggle in containing pulmonary infections in this disorder. Physiotherapy may lead to a transient fall in the arterial oxygen as can sessions of nebuliser therapy which precedes physiotherapy. The originality of the system studied and proposed here for the administration of medication depends on an electronic control which guarantees that there is the nebulisation of a constant volume of medication with each inspiration. Triggered by inspiration the active principle nebulised is perfectly co-ordinated to the inspiratory cycle. A comparative chromatography carried out in this slides of silica-gel have enabled us to verify the absence of any degradation of the active principle contained in the nebuliser solution during the ten minutes period of aerosol therapy. Thus a quantification of the administered dose of Amiloride Chlorhydrate is made possible. In association with oxygen it enables an efficacious preparation of respiratory physiotherapy to children. As the expiratory tubing ends in a filter the fraction of the oxygen inhaled by the patient remains very high; 80% (V/V) of the medication is emitted in the form of liquid particles whose diameter lies between 0.5 and 5 micrometers. In practice in order to humidify the sputum and to restore the oximetry before the physiotherapy sessions, it seemed to us an interesting possibility to administer Amiloride Chlorhydrate and oxygen simultaneously. This is achieved in hospital by using wall-mounted oxygen (at a gas pressure of 3.5 bars).(ABSTRACT TRUNCATED AT 250 WORDS)
